Large panel genetic testing produces more questions than answers in breast cancer

Date:

May 14, 2014

Source:

Perelman School of Medicine at the University of Pennsylvania

Summary:

While large genetic testing panels promise to uncover clues about patients’ DNA, a team of researchers has found that those powerful tests tend to produce more questions than they answer. Large genetic testing panels sometimes reveal mutations in genes that are associated with an increased risk in developing cancer. BRCA 1 and BRCA 2 genes are prime examples, where women can opt for mastectomies and ovary removal surgery -- which research shows slashes their risk of developing those cancers. However, there is not yet guidance for clinicians on how to care for patients who exhibit other types of mutations, such as CHEK2 and ATM.

Share:

Total shares:

FULL STORY

While large genetic testing panels promise to uncover clues about patients' DNA, a team of researchers from Penn Medicine's Abramson Cancer Center (ACC) has found that those powerful tests tend to produce more questions than they answer. In a study of 278 women with early onset breast cancer who did not have the BRCA genes, the researchers found that only 2.5 percent of the patients had inherited mutations that were actually clinically actionable. Experts don't yet know how to interpret most of the mutations discovered by the test -- known as massively parallel gene sequencing.

Results of the study, led by author Kara Maxwell, MD, PhD, a fellow in the division of Hematology-Oncology in the Perelman School of Medicine at the University of Pennsylvania, will be presented during the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago in early June.

Large genetic testing panels sometimes reveal mutations in genes that are associated with an increased risk in developing cancer. BRCA 1 and BRCA 2 genes are prime examples, where women can opt for mastectomies and ovary removal surgery -- which research shows slashes their risk of developing those cancers. However, there is not yet guidance for clinicians on how to care for patients who exhibit other types of mutations, such as CHEK2 and ATM. These are known as variants of unknown significance (VUS).

"We're in a time where the testing technology has outpaced what we know from a clinical standpoint. There's going to be a lot of unknown variants that we're going to have to deal with as more patients undergo large genetic testing panels," said Maxwell. "It's crucial that we figure out the right way to counsel women on these issues, because it can really provoke a lot of anxiety for a patient when you tell them, 'We found a change in your DNA and we don't know what it means.'"

The team, which includes Susan Domchek, MD, the Basser Professor in Oncology and director of the Basser Research Center for BRCA in Penn's ACC, and Katherine Nathanson, MD, an associate professor in the division of Translational Medicine and Chief Oncogenomics Physician for the ACC, studied 278 patients who had been diagnosed with breast cancer under the age of 40, were not carriers of the BRCA1 or BRCA2 mutations, and had no family history of ovarian cancer.

The researchers performed massively parallel gene sequencing to detect 22 known or proposed breast cancer susceptibility genes in each woman. Though the testing did reveal multiple variants of genes that are known to confer increased risk of breast cancer in patients who develop the disease young, only 2.5 percent of patients tested were found to have mutations that are actionable under current treatment guidelines, including TP53, CDKN2A, MSH2, and MUTYH.

In all, the sequencing revealed reportable variants in over 30 percent of the patients.

"Knowing there is a mutation may not help us any more than knowing that the person has a positive family history -- which we already know," Nathanson said. "We don't know yet what to do with the information on an individual basis, and there certainly are no clinical standards."

This field of research is especially important when dealing with families who appear to have genetic predisposition to breast or other cancers but don't carry BRCA1/2 mutations, Maxwell said.

"We need to be very careful with how we use this data," Maxwell said. "You could be taking someone who thinks they're not at risk and making them at risk, or taking someone who is believed to be at risk and relieving them of that risk, but we don't know enough yet to be confident in our assessments of these findings."

Perelman School of Medicine at the University of Pennsylvania. "Large panel genetic testing produces more questions than answers in breast cancer." ScienceDaily. ScienceDaily, 14 May 2014. <www.sciencedaily.com/releases/2014/05/140514182532.htm>.

Perelman School of Medicine at the University of Pennsylvania. (2014, May 14). Large panel genetic testing produces more questions than answers in breast cancer. ScienceDaily. Retrieved August 2, 2015 from www.sciencedaily.com/releases/2014/05/140514182532.htm

Perelman School of Medicine at the University of Pennsylvania. "Large panel genetic testing produces more questions than answers in breast cancer." ScienceDaily. www.sciencedaily.com/releases/2014/05/140514182532.htm (accessed August 2, 2015).

July 31, 2015  School is just around the corner, which means backpacks and packed lunches await your children. One expert offers tips for parents to promote healthy dental habits while away from ... read more

July 29, 2015  By blocking the expression of a certain gene in patients, researchers have contributed to the demonstration of great decreases in the concentration of triglycerides in their ... read more

July 29, 2015  Viewing aquarium displays led to noticeable reductions in blood pressure and heart rate, a research team found in the first study of its kind. They also noted that higher numbers of fish helped to ... read more

May 27, 2015  While advances in technology have made multigene testing, or 'panel testing,' for genetic mutations that increase the risk of breast or other cancers an option, authors of a review say ... read more

Apr. 15, 2015  Recent media attention has focused on American actress Angelina Jolie's decision to have her ovaries and fallopian tubes surgically removed after genetic testing for such cancers. A study ... read more

Dec. 23, 2014  Whole-genome sequencing can be used to identify patients' risk for hereditary cancer, researchers have demonstrated. This is the first study that has used whole-genome sequencing to evaluate a ... read more

Nov. 27, 2013  Women who are members of families with BRCA2 mutations but who test negative for the family-specific BRCA2 mutations are still at greater risk for developing breast cancer compared with women in the ... read more